Skip to main content
NCBI home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2010 Apr 8;26(2):140–146. doi: 10.1007/s12264-010-0609-9

Preventive effect of estrogen on depression-like behavior induced by chronic restraint stress

雌激素在慢性束缚应激性抑郁发生中的作用

Wei Li 1, Qing-Jiao Li 1, Shu-Cheng An 1,✉
PMCID: PMC5560369  PMID: 20332819

Abstract

Objective

To investigate the roles of estrogen and kalirin-7 in chronic restraint stress (CRS)-induced depression and the pathophysiological mechanism of depression.

Methods

Healthy female mice from Institute of Cancer Research (ICR) were randomly divided into 3 groups: control group, CRS group, and estrogen + CRS group. CRS was used to establish the animal model of depression. Forced swimming test and immunohistochemistry method were utilized to investigate the animal behavior and kalirin-7 expression in the hippocampus, respectively.

Results

Compared with the control group, the CRS mice displayed depression-like behaviors, including a significant reduction in body weight, a significant increase in immobility time in forced swimming test, and a dramatic decrease in kalirin-7 expression in the hippocampus. However, administration of estrogen attenuated the CRS-induced negative behaviors, and simultaneously increased kalirin-7 expression.

Conclusion

Estrogen replacement therapy (ERT) could prevent CRS-induced depression-like behaviors in female ICR mice. Besides, kalirin-7 also plays a role in preventing CRS-induced depression-like behaviors.

Keywords: chronic restraint stress, depression, estrogen, neural plasticity, kalirin-7

References

  • [1].Holderbach R., Clark K., Moreau J.L., Bischofberger J., Normann C. Enhanced long-term synaptic depression in an animal model of depression. Biol Psychiatry. 2007;62(1):92–100. doi: 10.1016/j.biopsych.2006.07.007. [DOI] [PubMed] [Google Scholar]
  • [2].Ehlert U., Gaab J., Heinrichs M. Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: The role of the hypothalamus-pituitaryadrenal axis. Biol Psychol. 2001;57(1–3):141–152. doi: 10.1016/S0301-0511(01)00092-8. [DOI] [PubMed] [Google Scholar]
  • [3].Lopez J.F., Akil H., Watson S.J. Neural circuits mediating stress. Biol Psychiatry. 1999;46(11):1461–1471. doi: 10.1016/S0006-3223(99)00266-8. [DOI] [PubMed] [Google Scholar]
  • [4].Akil H.A., Morano M.I. Stress. In: Bloom F.E., Kupfer D.J., editors. Psychopharmacology: The fourth generation of progress. New York: Raven Press; 1995. pp. 773–785. [Google Scholar]
  • [5].Levine S. Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology. 2005;30(10):939–946. doi: 10.1016/j.psyneuen.2005.03.013. [DOI] [PubMed] [Google Scholar]
  • [6].Bowman R.E., Beck K.D., Luine V.N. Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Horm Behav. 2003;43(1):48–59. doi: 10.1016/S0018-506X(02)00022-3. [DOI] [PubMed] [Google Scholar]
  • [7].De Kloet E.R., Vreugdenhil E., Oitzl M.S., Joels M. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998;19(3):269–301. doi: 10.1210/er.19.3.269. [DOI] [PubMed] [Google Scholar]
  • [8].McEwen B.S. The neurobiology of stress: from serendipity to clinical relevance. Brain Res. 2000;886(1–2):172–189. doi: 10.1016/S0006-8993(00)02950-4. [DOI] [PubMed] [Google Scholar]
  • [9].Sapolsky R.M., Krey L.C., McEwen B.S. Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci U S A. 1984;81(19):6174–6177. doi: 10.1073/pnas.81.19.6174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Tsigos C., Chrousos G.P. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–871. doi: 10.1016/S0022-3999(02)00429-4. [DOI] [PubMed] [Google Scholar]
  • [11].Young E.A., Midgley A.R., Carlson N.E., Brown M.B. Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry. 2000;57(12):1157–1162. doi: 10.1001/archpsyc.57.12.1157. [DOI] [PubMed] [Google Scholar]
  • [12].Weissman M.M., Bland R.C., Canino G.J., Faravelli C., Greenwald S., Hwu H.G., et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA. 1996;276(4):293–299. doi: 10.1001/jama.276.4.293. [DOI] [PubMed] [Google Scholar]
  • [13].Hayward C., Sanborn K. Puberty and the emergence of gender differences in psychopathology. J Adolesc Health. 2002;30(4Suppl):49–58. doi: 10.1016/S1054-139X(02)00336-1. [DOI] [PubMed] [Google Scholar]
  • [14].Bloch M., Daly R.C., Rubinow D.R. Endocrine factors in the etiology of postpartum depression. Compr Psychiatry. 2003;44(3):234–246. doi: 10.1016/S0010-440X(03)00034-8. [DOI] [PubMed] [Google Scholar]
  • [15].Wittchen H.U., Hoyer J. Generalized anxiety disorder: nature and course. J Clin Psychiatry. 2001;62(11):15–19. [PubMed] [Google Scholar]
  • [16].Ahokas A., Kaukoranta J., Wahlbeck K., Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17β-estradiol: a preliminary study. J Clin Psychiatry. 2001;62(5):332–336. doi: 10.4088/JCP.v62n0504. [DOI] [PubMed] [Google Scholar]
  • [17].Frye C.A., Walf A.A. Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm Behav. 2002;41(3):306–315. doi: 10.1006/hbeh.2002.1763. [DOI] [PubMed] [Google Scholar]
  • [18].Frye C.A., Wawrzycki J. Effect of prenatal stress and gonadal hormone condition on depressive behaviors of female and male rats. Horm Behav. 2003;44(4):319–326. doi: 10.1016/S0018-506X(03)00159-4. [DOI] [PubMed] [Google Scholar]
  • [19].Estrada-Camarena E., Fernandez-Guasti A., Lopez-Rubalcava C. Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology. 2003;28(5):830–838. doi: 10.1038/sj.npp.1300097. [DOI] [PubMed] [Google Scholar]
  • [20].Nacher J., Pham K., Gil-Fernandez V., Mcewen B.S. Chronic restraint stress and chronic corticosterone treatment modulate differentially the expression of molecules related to structural plasticity in the adult rat piriform cortex. Neuroscience. 2004;126(2):503–509. doi: 10.1016/j.neuroscience.2004.03.038. [DOI] [PubMed] [Google Scholar]
  • [21].Fossati P., Radtchenko A., Boyer P. Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol. 2004;14(5):503–510. doi: 10.1016/j.euroneuro.2004.09.001. [DOI] [PubMed] [Google Scholar]
  • [22].Ziv N.E., Smith S.J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron. 1996;17(1):91–102. doi: 10.1016/S0896-6273(00)80283-4. [DOI] [PubMed] [Google Scholar]
  • [23].Fiala J.C., Feinberg M., Popov V., Harris K.M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J Neurosci. 1998;18(21):8900–8911. doi: 10.1523/JNEUROSCI.18-21-08900.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Alam M.R., Johnson R.C., Darlington D.N., Hand T.A., Mains R.E., Eipper B.A. Kalirin-7, a cytosolic protein with Spectrin-like and GDP/GTP exchange factor-like domains that interacts with Peptidylglycine α-amidating monooxygenase, and integral membrane peptideprocessing enzyme. J Biol Chem. 1997;272(19):12667–12675. doi: 10.1074/jbc.272.19.12667. [DOI] [PubMed] [Google Scholar]
  • [25].Johnson R.C., Penzes P., Eipper B.A., Mains R.E. Isoforms of Kalirin-7, a neuronal Dbl family member, generated through the use ofdifferent 50- and 30-ends along with an internal translational initiation site. J Biol Chem. 2000;275(25):19324–19333. doi: 10.1074/jbc.M000676200. [DOI] [PubMed] [Google Scholar]
  • [26].Penzes P., Johnson R.C., Alam M.R., Kambampati V., Mains R.E. An isoform of kalirin-7, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J Biol Chem. 2000;275(9):6395–6403. doi: 10.1074/jbc.275.9.6395. [DOI] [PubMed] [Google Scholar]
  • [27].Penzes P., Johnson R.C., Sattler R., Zhang X., Huganir R.L., Kambampati V., et al. The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron. 2001;29(1):229–242. doi: 10.1016/S0896-6273(01)00193-3. [DOI] [PubMed] [Google Scholar]
  • [28].Penzes P., Beeser A., Chernoff J., Schiller M.R., Eipper B.A., Mains R.E., et al. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin-7. Neuron. 2003;37(2):263–274. doi: 10.1016/S0896-6273(02)01168-6. [DOI] [PubMed] [Google Scholar]
  • [29].Porsolt R.D., Bertin A., Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977;299(2):327–336. [PubMed] [Google Scholar]
  • [30].Paxinos G., Watson C. The rat brain in stereotaxic coordinates. 4th edition. New York: Academic Press; 1998. [Google Scholar]
  • [31].Nemeroff C.B. The neurobiology of depression. Sci Am. 1998;278(6):42–49. doi: 10.1038/scientificamerican0698-42. [DOI] [PubMed] [Google Scholar]
  • [32].Zardooz H., Zahedi Asl S., Gharib Naseri M.K., Hedayati M. Effect of chronic restraint stress on carbohydrate metabolism in rat. Physiol Behav. 2006;89(3):373–378. doi: 10.1016/j.physbeh.2006.06.023. [DOI] [PubMed] [Google Scholar]
  • [33].Matthews K., Forbes N., Reid I.C. Sucrose consumption as an hedonic measure following chronic unpredictable mild stress. Physiol Behav. 1995;57(2):241–248. doi: 10.1016/0031-9384(94)00286-E. [DOI] [PubMed] [Google Scholar]
  • [34].Cryan J.F., Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov. 2005;4(9):775–790. doi: 10.1038/nrd1825. [DOI] [PubMed] [Google Scholar]
  • [35].Hunter A.J., Nolan P.M., Brown S.D. Towards new models of disease and physiology in the neurosciences: the role of induced and naturally occurring mutations. Hum Mol Genet. 2000;9(6):893–900. doi: 10.1093/hmg/9.6.893. [DOI] [PubMed] [Google Scholar]
  • [36].Nestler E.J., Gould E., Manji H., Buncan M., Duman R.S., Greshenfeld H.K., et al. Preclinical models: status of basic research in depression. Biol Psychiatry. 2002;52(6):503–528. doi: 10.1016/S0006-3223(02)01405-1. [DOI] [PubMed] [Google Scholar]
  • [37].Gregus A., Wintink A.J., Davis A.C., Kalynchuk L.E. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res. 2005;156(1):105–114. doi: 10.1016/j.bbr.2004.05.013. [DOI] [PubMed] [Google Scholar]
  • [38].Duman R.S., Malberg J., Thome J. Neural plasticity to stress and antidepressant treatment. Biol Psychiatry. 1999;46(9):1181–1191. doi: 10.1016/S0006-3223(99)00177-8. [DOI] [PubMed] [Google Scholar]
  • [39].Manji H.K., Duman R.S. Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull. 2001;35(2):5–49. [PubMed] [Google Scholar]
  • [40].Ma X.M., Johnson R.C., Mains R.E., Eipper B.A. Expression of kalirin-7, a neuronal GDP/GTP exchange factor of the trio family, in the central nervous system of the adult rat. J Comp Neurol. 2001;429(3):388–402. doi: 10.1002/1096-9861(20010115)429:3<388::AID-CNE3>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  • [41].Ma X.M., Huang J., Wang Y., Eipper B.A., Mains R.E. Kalirin-7, a multifunctional Rho uanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines. J Neurosci. 2003;23(33):10593–10603. doi: 10.1523/JNEUROSCI.23-33-10593.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES